The Role of Hormones in the Menstrual Cycle
The menstrual cycle is a complex collection of metabolic processes. It is regulated by the interactions of both pituitary and ovarian hormones (Radovick et al., 2012). While reference will be made to several of these hormones, this essay will focus primarily on the pituitary hormone Luteinising Hormone (LH) and the ovarian hormone Oestrogen. The bulk of detail is given over to examining their roles and functions within the reproductive cycle. Finally, the possible results of what happens in cases when their balance within the body is detrimentally altered will be examined.
Overview of the Female Reproductive Cycle
Menstruation can be divided into three distinct phases over which two separate, yet complimentary cycles occur simultaneously. The ovarian cycle (figure 1) concerns the growth of a new follicle and ovulation, and it consists of two phases – the follicular phase and the luteal phase. The uterine cycle (figure 2) concerns the thickening and loss of the uterine endometrium. Taken together, the whole menstrual cycle can be divided into the menstrual, proliferative and secretory phases.
Figure 1: The hormones and associated follicle development stages of the ovarian cycle.
The reproductive cycle begins with the menstrual flow phase or mensus; in response to declining levels of oestrogen and progesterone, the previously thickened endometrium of the uterus disintegrates and menstrual bleeding occurs. During this time, stimulated by Follicle Stimulating Hormone (FSH) and LH, a new follicle begins to grow within the ovary. As it does so, it releases low levels of oestrogen which initiates the proliferation and thickening of the endometrial lining of the uterus (figure 2), thus this process is termed the proliferative phase.
Figure 2: Hormones and their associated affects on the endometrium during the uterine cycle.
Once the follicle has grown to a certain size (around day 14 of the cycle), it produces a surge of oestrogen which in turn triggers a spike in LH production from the anterior pituitary. This LH surge finalises maturation of the follicle and initiates ovulation (Campbell, 2005). Figure 3 shows the mature oocyte being ejected from the mature (graafian) follicle. While the picture is without scale, the average size of the human oocyte is approximately 100mm. Ovulation marks the end of the proliferative phase and the beginning of the secretory phase of the uterine cycle.
Continued stimulation of the follicle by LH leads formation of the corpus luteum. The corpus luteum continues to produce oestrogen, though in greater volume than its follicular predecessor. In addition, progesterone is also produced which, along with the oestrogen, continues to promote the thickening of the endometrium and further inhibit the production of FSH & LH by inhibiting the production of Gonadotropin-releasing Hormone (GnRH) from the hypothalamus.
Eventually, as the cycle comes to an end, the corpus luteum will degenerate and, in the absence of a fertilised embryo to initiate alternative production pathways, the levels of oestrogen and progesterone will decline leading once more to mensus.
As noted above, there are several different hormones involved in the regulation of the menstrual cycle. The hormones discussed here are only the most prominent in the cycle.
Gonadotropin-Releasing Hormone (GnRH)
Released by the hypothalamus, GnRH stimulates the anterior pituitary gland to release FSH and LH.
As the name suggests, gonadotropin hormones are involved with ovarian (in females) growth.
Follicle Stimulating Hormone (FSH)
FSH specifically stimulates the initial development of dormant ovarian follicles within the ovary. It also contributes to continued development of the follicle in conjunction with LH.
Luteinising Hormone (LH)
Initially, LH encourages growth of stimulated follicles within the ovary (figure 4). Several follicles will begin to mature, but usually only one becomes the dominant follicle (Tortora, 2009).
Both FSH and LH combine to stimulate the production of oestrogen by the ovarian follicle by the following action:
One type of cell in the follicle (theca cells), under the influence of LH produce androgens.
A second type of follicle cells (granulosa cells), stimulated by FSH, take up these androgens and convert them into oestrogens.
A significant peak in LH triggers ovulation and further stimulation of the graafian follicle by LH causes the formation of the corpus luteum, as in figure 1.
Figure 4: Menstrual & Proliferation phase hormone action.
Being a group of at least six hormones (Tortora, 2009), oestrogens perform a number of regulatory roles, both inhibitory and stimulatory (Radovick et al., 2012) within the reproductive cycle (Table 1).
Secreted initially by the growing ovarian follicle, and afterwards by the resulting corpus luteum, their effects within the reproductive cycle are primarily the proliferation of the uterine endometrium. The proliferation is a two-fold action, first by oestrogen affecting receptive cells and triggering proliferation, but also by increasing the receptiveness of the cells it interacts with to increase the rate of proliferation (Trickey, 2003).
At the initial low levels in the cycle, oestrogen inhibits excessive production of FSH and LH from the anterior pituitary (figure 4) and may also inhibit GnRH (Solomon, 2008; Radovick et al., 2012). This negative feedback is key to ensuring that only one dominant follicle is produced per cycle.
High levels of oestrogen – such as that produced by a mature ovarian follicle (aka graafian follicle) – stimulate the production of GnRH from the hypothalamus, thus creating a peak in FSH and LH from the anterior pituitary (which is no longer inhibited by low levels of oestrogen). The resultant surge in LH, as noted above, is what triggers ovulation (figure 1).
Table 1: Summarised data for LH & oestrogen.
Following development of the corpus luteum, increased levels of oestrogen and progesterone combine to inhibit GnRH production from the hypothalamus. This inhibits the release of FSH and LH from the anterior pituitary and so prevents the growth of another follicle in the ovary.
|Anterior Pituitary||Development of ovarian follicleDevelopment of Corpus Luteum||Production of oestrogen (indirect)|
|Preparation of uterine endometriumThins & increases pH of cervical mucus
Induces maturation of reproductive structures
In addition to the effects mentioned, oestrogens are also responsible for the thinning and increased pH of cervical mucus (Solomon, 2008), creating a less hostile environment for sperm. Out-with the reproductive cycle, oestrogens are responsible for the growth and maturation of sex organs at puberty.
Produced by the corpus luteum, progesterone acts alongside oestrogen to increase the thickness of the uterine endometrium and inhibit the production of GnRH from the hypothalamus.
In particular progesterone stimulates nutrient secretion from glands within the endometrium and finalises its preparation for the acceptance of a fertilized egg (Solomon, 2008).
Abnormalities & Disease
One of the most common afflictions to upset the menstrual cycle is the occurrence of ovarian cysts. There are a range of cysts that can form on the ovary and all have differing effects dependent upon how exactly they are formed. Given the delicate balancing act of hormone regulation in the menstrual cycle, anything that disrupts hormone levels can lead to complications.
Hormone Producing Ovarian Cysts
These variants consist of abnormal follicle cells that continue to produce hormones. Most common are those that produce oestrogen. The amount of oestrogen produced may not necessarily prevent the menstrual cycle from completing, but will often cause heavy or irregular mensus. Fluctuations in the oestrogen levels, over a long period, may also lead to further complications such as endometrial cancer (Trickey, 2003).
Polycystic Ovarian Syndrome (PCOS)
Despite the name, PCOS is a very complex condition that involves the formation of multiple ovarian follicles, rather than true cysts (Trickey, 2003) and presents in a wide spectrum of symptoms. One of the features of some patients with PCOS is hyper-secretion of Luteinising Hormone which can specifically lead to irregular menstrual cycles, infertility and increased chance of miscarriage (Balen, 1998; Homburg, 1998).
Beginning with the breakdown of the endometrium and the ending with the finalisation of its preparation, the menstrual cycle could be analogised as a trophy example of catabolic and anabolic metabolism within the body. It is a highly complex cycle involving many different metabolic pathways to bring about the myriad of tissue changes that occur. LH and oestrogen play key regulatory roles both individually and in conjunction with other hormones, as well as having dual roles of stimulation and inhibition, throughout the entire cycle (Table 1). Their role in the process is so involved that any upset of their balance can produce a wide number of detrimental effects ranging from the merely troubling to the life threatening.
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